title: Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway.
abstract: Exosomes are secreted cellular vesicles that can be internalized by dendritic cells (DCs), contributing to antigen-specific naive CD4(+) T-cell activation. Here, we demonstrate that human immunodeficiency virus type 1 (HIV-1) can exploit this exosome antigen-dissemination pathway intrinsic to mature DCs (mDCs) for mediating trans-infection of T lymphocytes. Capture of HIV-1, HIV-1 Gag-enhanced green fluorescent protein (eGFP) viral-like particles (VLPs), and exosomes by DCs was up-regulated upon maturation, resulting in localization within a CD81(+) compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway.
authors.affiliation: IrsiCaixa Foundation, Badalona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Mar
authors.initials: M
authors.lastname: Naranjo-Gómez
authors.forename: Jacob
authors.initials: J
authors.lastname: Archer
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hatch
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Francesc E
authors.initials: FE
authors.lastname: Borràs
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.forename: John H
authors.initials: JH
authors.lastname: Connor
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Fernández-Figueras
authors.forename: Landon
authors.initials: L
authors.lastname: Moore
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Suryaram
authors.initials: S
authors.lastname: Gummuluru
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000187:drug effects / Q000821:virology; D002518:Ceramides / Q000096:biosynthesis / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D055354:Exosomes / Q000737:chemistry / Q000502:physiology*; D037341:Fumonisins / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000821:virology; D007668:Kidney; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology; D021962:Membrane Microdomains / Q000737:chemistry / Q000502:physiology*; D011402:Pronase / Q000494:pharmacology; D060225:Tetraspanin 28; D053586:Virus Internalization; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000032:analysis
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; D002518:Ceramides; D037341:Fumonisins; D008563:Membrane Lipids; D060225:Tetraspanin 28; C485184:enhanced green fluorescent protein; D054301:gag Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; C056933:fumonisin B1; D011402:Pronase